Molecular prenatal diagnosis of Hb H Hydrops Fetalis caused by haemoglobin Adana and the implications to antenatal screening for alpha-thalassaemia

摘要

alpha-Thalassaemia results from a decrease in production of the alpha-globin component of haemoglobin and is a sub-group of the heterogeneous group of haemoglobin disorders known as the haemoglobinopathies. The severity of the defect in alpha-thalassaemia is very variable. At one extreme it is a completely asymptomatic condition resulting from the deletion or dysfunction of one of the four alpha-globin genes (alpha~+-thalassaemia trait). At the other extreme is haemoglobin Bart's hydrops fetalis (homozygousalpha~0-thalassaemia), which results from deletion of all four alpha-globin genes and is a condition that is generally incompatible with life (Weatherall and Clegg, 2001).Hb H disease is the severest form of alpha-thalassaemia compatible with post-natal life and occurs when alpha-thalassaemia mutations interact to reduce alpha-globin chain synthesis to approximately one-quarter of normal levels. The excess of beta-globin chain production over alpha-chain production leads to the formation of an abnormal haemoglobin comprised of beta-chain tetramers, which is referred to as Hb H. The most common form of Hb H disease is the deletional form, so called because it results from the deletion of three of the four alpha~0-globin genes. Patients are compound heterozygous for alpha~0-thalassaemia and alpha~+-thalassaemia deletion mutations. However, Hb H disease can also result from a patient having a deletion of two alpha-globin genes (alpha~0-thalassaemia trait) along with inactivation of a third gene by a non-deletion mutation (alpha~+-thalassaemia trait), or the interaction of two non-deletion mutations. This group of disorders is known as 'non-deletional' Hb H disease and is generally more severe than the deletional form; these disorders result in a critical reduction in alpha-globin chain synthesis, producing severe phenotypes requiring transfusions or which may even result in death (Hb H hydrops fetalis) (Chui et al., 2003).